The overall goal of this renewal of my mid-career award is to enhance my ability to train, mentor and support the career development of fellows and junior faculty in patient-oriented research in immunologic lung disease, in particular chronic beryllium disease (CBD) and HIV-induced lung disease. This proposal will insure that Dr. Fontenot continues to have adequate protected time to provide more opportunities for teaching and mentoring fellows and junior faculty. In addition, this protected time will allow Dr. Fontenot to participate in coursework that will enhance his leadership abilities, hone his skills in team science and enhance study design. During the previous funding period, my trainees have received 10 grants, including two R01s and a multi-PI U01 award, emphasizing my ability to successfully train mentees towards independence. With the support of my present K24, I have expanded my research portfolio to include the investigation of HIV-induced lung disease, and this renewal builds on my recently renewed R01 investigating pathogenic T cells in beryllium-induced disease and two U01s focused on the HIV-infected lung. For this renewal, the newly proposed research will consist of two specific aims focusing on CBD and HIV-induced disease in order to highlight the breadth of options that are available to trainees The first specific aim ill determine the peptide repertoire of HLA-DP2-expressing antigen-presenting cells before and after Be exposure and will investigate the hypothesis that Be2+ cations alter the repertoire of peptides capable of binding to HLA-DP2. In the second aim, we will investigate the hypothesis that Tropheryma whipplei is a true lung pathogen in HIV-infected subjects and contributes to loss of lung function. The mentoring plan will expand Dr. Fontenot's role in mentoring physician-scientists and other trainees in patient-oriented research. In addition, the research and mentoring plan will continue to leverage the resources and infrastructure present at the University of Colorado, including the Clinical Science Program and K12 Program in the Colorado Clinical and Translational Sciences Institute, an outstanding Department of Medicine with a long track record for successfully training physician-scientists, and long-standing collaborations that bridge basic immunology and patient-oriented research, to improve the quality of our patient's lives. With the continued support of this award, Dr. Fontenot will continu to lead translational lung immunology research and train the next generation of physician-scientists in lung immunology and pulmonary medicine.